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FLASH GENE
Symbol ITPR1 contributors: mct/npt - updated : 25-05-2016
HGNC name inositol 1,4,5-triphosphate receptor, type 1
HGNC id 6180
PROTEIN
PHYSICAL PROPERTIES Hydrophilic
STRUCTURE
motifs/domains
  • a N terminal cytoplasmic ligand binding domain linked by a modulatory domain to a channel forming hydrophobic domain made of six membrane-spanning segments near the C terminus (calcium channel)
  • ATP binding sites (GXGXXG sequence)
  • a IRBIT (inositol triphosphate receptor binding protein) domain
  • a central transducing/modulatory domain,
  • a C-terminal channel domain
    • conjugated ubiquitinated
    mono polymer homomer , tetramer
    HOMOLOGY
    Homologene
    FAMILY
  • INSP3 receptor family
    • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleolus
    text
  • intracellular membranes of platelets
  • coexpressed with RYR3
  • clustered at the node of Ranvier, in a distribution that is similar to the Nav1.6 sodium channels in the sciatic nerve
    • basic FUNCTION
  • inositol 1,4,5-triphosphate receptor, involved in Ca++ mobilization from the endoplastic reticulum
  • major neuronal member in the central nervous system
  • significantly decreases total Ca(2+) signals and terminates Ca(2+) oscillations
  • playing a predominant role in the function of the vascular smooth muscle
  • ITPR1 and ITPR3 may play a redundant role in the development of the second heart field (SHF)
  • ITPR1 localization, via protein EPB41L1, is necessary for Ca(2+) wave formation, which in turn mediates neurite formation
  • role for the HIF2A/ITPR1 axis in regulating Clear cell renal carcinomas cell survival
  • Ca(2+) release mediated by ITPR1 is an essential mechanism during the early steps of myoblast differentiation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text calcium ion transporter
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • constituent of heterotetrameric channel with ITPR2 and ITPR3
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to ITPR2, ITPR3, CABP1 (in the brain)
  • binding to CYCS during apoptosis
  • interacting with RYR1, RYR2, SHANK1, SHANK3 and TRPC4
  • interacting with TXNDC4 in a pH, redox-state and calcium-dependent manner
  • interacting with PKD2 (modulate intracellular Ca2+ signaling)
  • binding CIB1 (White 2006)
  • CABP1 interacting with ITPR1 in the brain through a Ca2+-induced binding of the CABP1 C-domain to the N-terminal region of ITPR1 (residues 1-587)
  • interaction juxtaposing the cytosolic RING domain of RNF170 with the cytosolic regions of activated ITPR1 that become ubiquitinated
  • interaction between FKBP1A and RYR1, RYR3 and ITPR1
  • ITPR1, ITPR2 enhanced gluconeogenic gene expression by promoting the calcineurin-mediated dephosphorylation of CRTC2
  • CA8 is an allosteric inhibitor of ITPR1, which regulates intracellular calcium release fundamental to critical cellular functions including neuronal excitability, neurite outgrowth, neurotransmitter release
  • DISC1 binds ITPR1 mRNA with ZNF385A, thereby regulating its dendritic transport for synaptic plasticity
  • calcium-release channel that is inositol 1,4,5-trisphosphate (IP3) responsive
    • cell & other
    REGULATION
    repressed by downregulated by muscarinic receptor activation
    Other highly sensitive to ATP mediating less regular Ca++ oscillations,in T lymphocyte
    phosphorylated by cAMP kinases
    regulated by TNF-alpha (in a neuronal environment modulates ITPR1 expression and intracellular Ca(2+) homeostasis) (Park 2009)
    RNF170, a E3 ligase, mediates ITPR1 ubiquitination
    ASSOCIATED DISORDERS
    corresponding disease(s) SCA16 , SCA15 , GLSPS2 , CLA4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in neurodegenerative disease (olivopontocerebellar atrophy, cerebellar atrophy of Holmes type, Alzheimers disease, Friedreich's ataxia, cerebellopontine ataxia)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    CA8 and ITPR1 represent new therapeutic targets for chronic pain
    ANIMAL & CELL MODELS
  • mice with complete homozygosity for Itpr1 ablation suffer from severe epilepsy and ataxia and die either in utero or before weaning